Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

Chiara Bellocchi, Álvaro Fernández-Ochoa, Gaia Montanelli, Barbara Vigone, Alessandro Santaniello, Rosa Quirantes-Piné, Isabel Borrás-Linares, Maria Gerosa, Carolina Artusi, Roberta Gualtierotti, Antonio Segura-Carrettero, Marta E Alarcón-Riquelme, Lorenzo Beretta

Research output: Contribution to journalArticle

Abstract

Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren's syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.

Original languageEnglish
Article numberE1291
JournalJournal of Clinical Medicine
Volume8
Issue number9
DOIs
Publication statusPublished - Aug 23 2019

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Metabolomics
Autoimmune Diseases
Bacteria
Butyrates
ROC Curve
Systemic Lupus Erythematosus
Dysbiosis
Prevotella
Metabolome
Microbiota
rRNA Genes
Connective Tissue
Mass Spectrometry
Phospholipids
High Pressure Liquid Chromatography

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Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases. / Bellocchi, Chiara; Fernández-Ochoa, Álvaro; Montanelli, Gaia; Vigone, Barbara; Santaniello, Alessandro; Quirantes-Piné, Rosa; Borrás-Linares, Isabel; Gerosa, Maria; Artusi, Carolina; Gualtierotti, Roberta; Segura-Carrettero, Antonio; Alarcón-Riquelme, Marta E; Beretta, Lorenzo.

In: Journal of Clinical Medicine, Vol. 8, No. 9, E1291, 23.08.2019.

Research output: Contribution to journalArticle

Bellocchi, C, Fernández-Ochoa, Á, Montanelli, G, Vigone, B, Santaniello, A, Quirantes-Piné, R, Borrás-Linares, I, Gerosa, M, Artusi, C, Gualtierotti, R, Segura-Carrettero, A, Alarcón-Riquelme, ME & Beretta, L 2019, 'Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases', Journal of Clinical Medicine, vol. 8, no. 9, E1291. https://doi.org/10.3390/jcm8091291
Bellocchi, Chiara ; Fernández-Ochoa, Álvaro ; Montanelli, Gaia ; Vigone, Barbara ; Santaniello, Alessandro ; Quirantes-Piné, Rosa ; Borrás-Linares, Isabel ; Gerosa, Maria ; Artusi, Carolina ; Gualtierotti, Roberta ; Segura-Carrettero, Antonio ; Alarcón-Riquelme, Marta E ; Beretta, Lorenzo. / Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases. In: Journal of Clinical Medicine. 2019 ; Vol. 8, No. 9.
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AU - Santaniello, Alessandro

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AU - Borrás-Linares, Isabel

AU - Gerosa, Maria

AU - Artusi, Carolina

AU - Gualtierotti, Roberta

AU - Segura-Carrettero, Antonio

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N2 - Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren's syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.

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